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BACKGROUND: Postoperative pancreatic fistula (POPF) is a critical complication of laparoscopic gastrectomy (LG). However, there are no widely recognized anatomical landmarks to prevent POPF during LG. This study aimed to identify anatomical landmarks related to POPF occurrence during LG for gastric cancer and to develop an artificial intelligence (AI) navigation system for indicating these landmarks. METHODS: Dimpling lines (DLs)-depressions formed between the pancreas and surrounding organs-were defined as anatomical landmarks related to POPF. The DLs for the mesogastrium, intestine, and transverse mesocolon were named DMP, DIP, and DTP, respectively. We included 50 LG cases to develop the AI system (45/50 were used for training and 5/50 for adjusting the hyperparameters of the employed system). Regarding the validation of the AI system, DLs were assessed by an external evaluation committee using a Likert scale, and the pancreas was assessed using the Dice coefficient, with 10 prospectively registered cases. RESULTS: Six expert surgeons confirmed the efficacy of DLs as anatomical landmarks related to POPF in LG. An AI system was developed using a semantic segmentation model that indicated DLs in real-time when this system was synchronized during surgery. Additionally, the distribution of scores for DMP was significantly higher than that of the other DLs (p < 0.001), indicating the relatively high accuracy of this landmark. In addition, the Dice coefficient of the pancreas was 0.70. CONCLUSIONS: The DLs may be used as anatomical landmarks related to POPF occurrence. The developed AI navigation system can help visualize the DLs in real-time during LG.
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BACKGROUND: Although findings from drip infusion cholangiography with computed tomography (DIC-CT) are useful in preoperative anatomic evaluation for laparoscopic cholecystectomy (LC), their relationship with intraoperative surgical difficulty based on the difficulty score (DS) proposed by Tokyo Guidelines 2018 is unclear. We examined this relationship. METHODS: Data were collected from 202 patients who underwent LC for benign gallbladder (GB) disease with preoperative DIC-CT in our department. DIC-CT findings were classified into GB-positive and GB-negative groups based on GB opacification, and clinical characteristics were compared. DS assessed only on findings from around Calot's triangle was considered "cDS", and patients were divided into cDS ≤2 and ≥3 groups. Preoperative data including DIC-CT findings were evaluated using multivariate analysis. RESULTS: DIC-CT findings showed 151 (74.8%) GB-positive and 51 (25.2%) GB-negative patients. Surgical outcomes were significantly better in the GB-positive versus GB-negative group for operation time (107 vs. 154 min, p < .001), blood loss (8 vs. 25 mL, p < .001), cDS (0.8 vs. 2.2, p < .001), and critical view of safety score (4.0 vs. 3.1, p < .001). cDS was ≤2 in 174 (86.1%) and ≥3 in 28 (13.9%) patients. By multivariate analysis, DIC-CT findings and alkaline phosphatase values were independent factors predicting intraoperative difficulty. CONCLUSION: DIC-CT findings are useful for predicting cDS in LC.
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BACKGROUND: A stapler is usually used for transection and closure of the pancreas in distal pancreatectomy (DP) or central pancreatectomy (CP). When the pancreas is transected to the right of the portal vein, it is difficult to use a stapler and clinically relevant postoperative pancreatic fistula (CR-POPF) frequently occurs. We report on the efficacy of pancreaticojejunostomy (PJ) of the pancreatic stump for patients in whom stapler use is difficult. METHODS: Patients who underwent DP or CP were enrolled in this study. The pancreas was usually transected by a stapler, and ultrasonic coagulating shears (UCS) were used depending on the tumor situation. When using UCS, hand-sewn closure or PJ was performed for the pancreatic stump. The relationship between clinicopathological factors and the methods of pancreatic transection and closure were investigated. RESULTS: In total, 164 patients underwent DP or CP, and the pancreas was transected with a stapler in 150 patients and UCS in 14 patients. The rate of CR-POPF was higher and the postoperative hospital stay was longer in the UCS group than in the stapler group. PJ of the pancreatic stump, which was performed for 7 patients, did not worsen intraoperative factors. CR-POPF was not seen in these 7 patients, which was significantly less than that with hand-sewn closure. CONCLUSIONS: PJ of the pancreatic stump during DP or CP reduces CR-POPF compared with hand-sewn closure and may be useful especially when the pancreas is transected to the right of the portal vein.
Subject(s)
Pancreatectomy , Pancreatic Fistula , Pancreatic Neoplasms , Pancreaticojejunostomy , Humans , Pancreaticojejunostomy/methods , Pancreatectomy/methods , Male , Female , Middle Aged , Aged , Pancreatic Fistula/prevention & control , Pancreatic Fistula/etiology , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms/pathology , Adult , Treatment Outcome , Postoperative Complications/prevention & control , Postoperative Complications/etiology , Retrospective Studies , Aged, 80 and over , Surgical Stapling , Length of Stay , Surgical Staplers , Suture TechniquesABSTRACT
PURPOSE: Obesity is known to be associated with colorectal adenoma (CRA) and colorectal cancer (CRC); yet colonoscopy is not considered an essential preoperative evaluation before bariatric/metabolic surgery. The aim of this study was to clarify the clinical significance of preoperative colonoscopy for obese Japanese patients. METHODS: The subjects of this retrospective study were 114 patients who underwent screening colonoscopy before bariatric/metabolic surgery. Multivariate analyses were performed to evaluate the independent predictors of CRA/CRC among the characteristics identified as significant or nearly significant by univariate analyses. RESULTS: Colonoscopy revealed abnormal findings indicating the need for biopsy or polypectomy in 20 of the 114 patients (17.5%), and CRA was diagnosed in 13 patients (11.4%). Three patients (2.6%), who were all ≥ 56 years old, had a CRA ≥ 10 mm in diameter. The multivariate analysis showed that older age and male sex were significant predictors of CRA/CRC, which was identified in 46.2% of the male patients aged ≥ 46 years. CONCLUSION: Our findings suggest that older age and male sex may be risk factors for CRA/CRC in obese Japanese candidates for bariatric/metabolic surgery; thus, preoperative colonoscopy should be considered for these high-risk patients.
Subject(s)
Adenoma , Bariatric Surgery , Colorectal Neoplasms , Laparoscopy , Humans , Male , Middle Aged , Retrospective Studies , Clinical Relevance , Japan/epidemiology , Colonoscopy/adverse effects , Risk Factors , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/surgery , Colorectal Neoplasms/pathology , Obesity/complications , Obesity/epidemiology , Adenoma/diagnosis , Adenoma/surgery , Laparoscopy/adverse effectsABSTRACT
BACKGROUND: Multidisciplinary therapy centered on antitumor drugs is indicated in patients with unresectable pancreatic neuroendocrine tumors (PanNET). However, the criteria for selection of optimal therapeutic agents is controversial. The aim of this study was to assess the malignancy of PanNET for optimal therapeutic drug selection. METHODS: Forty-seven patients with PanNET who underwent surgery were reviewed retrospectively, and immunohistochemical characteristics, including expression of GLUT1, SSTR2a, SSTR5, Survivin, X-chromosome-linked inhibitor of apoptosis protein (XIAP), and Caspase3 in the resected specimens, were investigated. Relapse-free survival (RFS) and overall survival (OS) were evaluated with regard to the characteristics using the Kaplan-Meier method and compared with the log-rank test. RESULTS: GLUT1 expression showed significant correlation with sex (p = 0.036) and mitotic rate (p = 0.048). Survivin and XIAP expression showed significant correlation with T-stage (p = 0.014 and 0.009), p-Stage (p = 0.028 and 0.045), and mitotic rate (p = 0.023 and 0.007). XIAP expression also significantly influenced OS (p = 0.044). CONCLUSIONS: Survivin and XIAP correlated with grade of malignancy, and expression of XIAP in particular was associated with a poor prognosis. Expression of these proteins may be a useful indicator to select optimal therapeutic agents in PanNET.
Subject(s)
Neuroendocrine Tumors , Pancreatic Neoplasms , Humans , Survivin/metabolism , Survivin/therapeutic use , Inhibitor of Apoptosis Proteins/metabolism , Inhibitor of Apoptosis Proteins/therapeutic use , Retrospective Studies , Glucose Transporter Type 1 , Prognosis , Neoplasm Recurrence, Local , X-Linked Inhibitor of Apoptosis Protein/metabolism , X-Linked Inhibitor of Apoptosis Protein/therapeutic use , Apoptosis , Pancreatic Neoplasms/pathologyABSTRACT
BACKGROUND: Laparoscopic repeat hepatectomy (LRH) has increased, but appropriate indications for LRH are unclear. This study aimed to clarify appropriate indications for LRH. METHODS: We retrospectively compared surgical outcomes between open RH (ORH) (n = 57) and LRH (n = 40) groups. To detect difficult cases of complete pure LRH, we examined patients with unplanned intraoperative hand-assisted laparoscopic surgery (HALS)/open conversion (n = 6). RESULTS: In the LRH versus ORH group, as previous hepatectomy, laparoscopic (75% vs. 12%, p < 0.001) and partial hepatectomy (Hr0) (73% vs. 37%, p = 0.002) were more frequently performed, and as RH procedure, partial hepatectomy (Hr0) (88% vs. 47%, p = 0.0002) was more frequently performed. S1 tumor cases were higher in ORH group (11% vs. 0%), but S2-6 cases were higher in LRH group (73% vs. 49%) (p = 0.02). In LRH group, compared to the pure LRH patients, HALS/open conversion patients underwent significantly more previous hepatectomy with more than lobectomy (Hr2-3) (33% vs. 2.9%, p = 0.033) and more RH procedures with segmentectomy (HrS) (33% vs. 2.9%, p = 0.03). All LRH requiring a repeat hepatic hilar approach were HALS conversions. CONCLUSION: Appropriate indications for LRH were previous hepatectomy was laparoscopic partial hepatectomy (Hr0), and RH procedure was partial hepatectomy (Hr0) for S2-6 tumor location. When RH is more than segmentectomy (HrS) requiring a repeat hepatic hilar approach, planned HALS or ORH may be a better approach than pure LRH.
Subject(s)
Laparoscopy , Liver Neoplasms , Humans , Hepatectomy/methods , Liver Neoplasms/surgery , Retrospective Studies , Laparoscopy/methods , Length of Stay , Treatment OutcomeABSTRACT
BACKGROUND: The Critical View of Safety (CVS) was proposed in 1995 to prevent bile duct injury during laparoscopic cholecystectomy (LC). The achievement of CVS was evaluated subjectively. This study aimed to develop an artificial intelligence (AI) system to evaluate CVS scores in LC. MATERIALS AND METHODS: AI software was developed to evaluate the achievement of CVS using an algorithm for image classification based on a deep convolutional neural network. Short clips of hepatocystic triangle dissection were converted from 72 LC videos, and 23,793 images were labeled for training data. The learning models were examined using metrics commonly used in machine learning. RESULTS: The mean values of precision, recall, F-measure, specificity, and overall accuracy for all the criteria of the best model were 0.971, 0.737, 0.832, 0.966, and 0.834, respectively. It took approximately 6 fps to obtain scores for a single image. CONCLUSIONS: Using the AI system, we successfully evaluated the achievement of the CVS criteria using still images and videos of hepatocystic triangle dissection in LC. This encourages surgeons to be aware of CVS and is expected to improve surgical safety.
Subject(s)
Cholecystectomy, Laparoscopic , Surgeons , Humans , Cholecystectomy, Laparoscopic/methods , Artificial Intelligence , Video Recording , Videotape RecordingABSTRACT
BACKGROUND: According to the National Clinical Database of Japan, the incidence of bile duct injury (BDI) during laparoscopic cholecystectomy has hovered around 0.4% for the last 10 years and has not declined. On the other hand, it has been found that about 60% of BDI occurrences are due to misidentifying anatomical landmarks. However, the authors developed an artificial intelligence (AI) system that gave intraoperative data to recognize the extrahepatic bile duct (EHBD), cystic duct (CD), inferior border of liver S4 (S4), and Rouviere sulcus (RS). The purpose of this research was to evaluate how the AI system affects landmark identification. METHODS: We prepared a 20-s intraoperative video before the serosal incision of Calot's triangle dissection and created a short video with landmarks overwritten by AI. The landmarks were defined as landmark (LM)-EHBD, LM-CD, LM-RS, and LM-S4. Four beginners and four experts were recruited as subjects. After viewing a 20-s intraoperative video, subjects annotated the LM-EHBD and LM-CD. Then, a short video is shown with the AI overwriting landmark instructions; if there is a change in each perspective, the annotation is changed. The subjects answered a three-point scale questionnaire to clarify whether the AI teaching data advanced their confidence in verifying the LM-RS and LM-S4. Four external evaluation committee members investigated the clinical importance. RESULTS: In 43 of 160 (26.9%) images, the subjects transformed their annotations. Annotation changes were primarily observed in the gallbladder line of the LM-EHBD and LM-CD, and 70% of these shifts were considered safer changes. The AI-based teaching data encouraged both beginners and experts to affirm the LM-RS and LM-S4. CONCLUSION: The AI system provided significant awareness to beginners and experts and prompted them to identify anatomical landmarks linked to reducing BDI.
Subject(s)
Abdominal Injuries , Bile Duct Diseases , Bile Ducts, Extrahepatic , Cholecystectomy, Laparoscopic , Humans , Cholecystectomy, Laparoscopic/adverse effects , Cholecystectomy, Laparoscopic/methods , Artificial Intelligence , Bile Ducts, Extrahepatic/surgery , Cystic Duct , Bile Ducts/injuriesABSTRACT
AIM: The number of surgeries for pancreatic ductal adenocarcinoma (PDAC) in older adults has been rising. This study aimed to evaluate the technical and oncological safety of pancreatectomy for older adults aged ≥75 years with PDAC by retrospectively comparing their short- and long-term outcomes with those of younger adults aged <75 years. METHODS: Data were collected from 117 patients who underwent pancreatectomy for PDAC in our department. The indication for surgery regarding patient characteristics was considered according to each patient's American Society of Anesthesiologists physical status and Eastern Cooperative Oncology Group Performance Status Scale. Data of older adults (n = 32) were compared with those of younger adults (n = 85), and comprised patient background, surgical factors, postoperative course, histopathological factors and prognostic factors. Additionally, prognostic nutritional index values preoperatively and at 1 and 6 months postoperatively were compared between the two groups. RESULTS: Although American Society of Anesthesiologists physical status and comorbidities were worse in older adults, there were no significant differences in surgical factors, postoperative courses and histopathological factors between the two groups. The overall complication rate tended to be higher in older adults (40.6%) than in younger adults (29.4%). There were no differences in median lengths of recurrence-free survival and overall survival (older adults vs younger adults: 12 vs 13 months, P = 0.545, and 26 vs 20 months, P = 0.535, respectively) between the two groups. Furthermore, no significant differences were found in prognostic nutritional index preoperatively to 6 months after surgery. CONCLUSION: With careful determination of surgical indications, pancreatectomy for PDAC can be carried out with acceptable post-pancreatectomy morbidity in younger adults. Geriatr Gerontol Int 2023; 23: 531-536.
Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Humans , Aged , Retrospective Studies , Pancreatectomy/adverse effects , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms/pathology , Carcinoma, Pancreatic Ductal/surgery , Carcinoma, Pancreatic Ductal/pathology , Pancreatic NeoplasmsABSTRACT
BACKGROUND: Attention to anatomical landmarks in the appropriate surgical phase is important to prevent bile duct injury (BDI) during laparoscopic cholecystectomy (LC). Therefore, we created a cross-AI system that works with two different AI algorithms simultaneously, landmark detection and phase recognition. We assessed whether landmark detection was activated in the appropriate phase by phase recognition during LC and the potential contribution of the cross-AI system in preventing BDI through a clinical feasibility study (J-SUMMIT-C-02). METHODS: A prototype was designed to display landmarks during the preparation phase and Calot's triangle dissection. A prospective clinical feasibility study using the cross-AI system was performed in 20 LC cases. The primary endpoint of this study was the appropriateness of the detection timing of landmarks, which was assessed by an external evaluation committee (EEC). The secondary endpoint was the correctness of landmark detection and the contribution of cross-AI in preventing BDI, which were assessed based on the annotation and 4-point rubric questionnaire. RESULTS: Cross-AI-detected landmarks in 92% of the phases where the EEC considered landmarks necessary. In the questionnaire, each landmark detected by AI had high accuracy, especially the landmarks of the common bile duct and cystic duct, which were assessed at 3.78 and 3.67, respectively. In addition, the contribution to preventing BDI was relatively high at 3.65. CONCLUSIONS: The cross-AI system provided landmark detection at appropriate situations. The surgeons who previewed the model suggested that the landmark information provided by the cross-AI system may be effective in preventing BDI. Therefore, it is suggested that our system could help prevent BDI in practice. Trial registration University Hospital Medical Information Network Research Center Clinical Trial Registration System (UMIN000045731).
Subject(s)
Abdominal Injuries , Bile Duct Diseases , Cholecystectomy, Laparoscopic , Humans , Artificial Intelligence , Prospective Studies , Cystic Duct , Bile Ducts/injuries , Intraoperative Complications/prevention & controlABSTRACT
AIM: Laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) located in the posterosuperior segments (PS) have generally been considered more difficult than those for HCC in anterolateral segments (AL), but may be safe and feasible for selected patients with accumulated experience. In the present study, we investigated the effectiveness of LLR for single nodular HCCs ≤3 cm located in PS. METHODS: In total, 473 patients who underwent partial liver resection for single nodular HCCs ≤3 cm at the 18 institutions belonging to the Kyusyu Study Group of Liver Surgery from January 2010 to December 2018 were enrolled. The short-term outcomes of laparoscopic partial liver resection and open liver resection (OLR) for HCCs ≤3 cm, with subgroup analysis of PS and AL, were compared using propensity score-matching analysis. Furthermore, results were also compared between LLR-PS and LLR-AL. RESULTS: The original cohort of patients with HCC ≤3 cm included 328 patients with LLR and 145 with OLR. After matching, 140 patients with LLR and 140 with OLR were analyzed. Significant differences were found between groups in terms of volume of blood loss (median, 55 vs. 287 ml, p < 0.001), postoperative complications (0.71 vs. 8.57%, p = 0.003), and postoperative hospital stay (median, 9 vs. 14 days, p < 0.001). The results of subgroup analysis of PS were similar. Short-term outcomes did not differ significantly between LLR-PS and LLR-AL after matching. CONCLUSIONS: Laparoscopic partial resection could be the preferred option for single nodular HCCs ≤3 cm located in PS.
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BACKGROUND: The prognosis of distal cholangiocarcinoma (dCCA) remains poor; thus, the identification of new therapeutic targets is warranted. Phosphorylated S6 ribosomal protein indicates a mammalian target of rapamycin complex 1 (mTORC1) activity, and mTORC1 plays a central role in controlling cell growth and regulating glucose metabolism. We aimed to clarify the effect of S6 phosphorylation on tumor progression and the glucose metabolic pathway in dCCA. METHODS: Thirty-nine patients with dCCA who underwent curative resection were enrolled in this study. S6 phosphorylation and the expression of GLUT1 were evaluated by immunohistochemistry, and their relationship with clinical factors was investigated. The effect of S6 phosphorylation on glucose metabolism with PF-04691502 treatment, an inhibitor of S6 phosphorylation, was examined in cancer cell lines by Western blotting and metabolomics analysis. Cell proliferation assays were performed with PF-04691502. RESULTS: S6 phosphorylation and the expression of GLUT1 were significantly higher in patients with an advanced pathological stage. Significant correlations between GLUT1 expression, S6 phosphorylation, and SUV-max of FDG-PET were shown. In addition, cell lines with high S6 phosphorylation levels showed high GLUT1 levels, and the inhibition of S6 phosphorylation reduced the expression of GLUT1 on Western blotting. Metabolic analysis revealed that inhibition of S6 phosphorylation suppressed pathways of glycolysis and the TCA cycle in cell lines, and then, cell proliferation was effectively reduced by PF-04691502. CONCLUSION: Upregulation of glucose metabolism via phosphorylation of S6 ribosomal protein appeared to play a role in tumor progression in dCCA. mTORC1 may be a therapeutic target for dCCA.
Subject(s)
Cholangiocarcinoma , TOR Serine-Threonine Kinases , Humans , Phosphorylation , TOR Serine-Threonine Kinases/metabolism , Glucose Transporter Type 1/metabolism , Ribosomal Proteins/metabolism , Up-Regulation , Glucose/metabolism , Mechanistic Target of Rapamycin Complex 1/metabolismABSTRACT
BACKGROUND: This study aims to clarify the perioperative risk factors and short-term prognosis of central bisectionectomy (CB) for hepatocellular carcinoma (HCC). METHODS: Surgical data from 142 selected patients out of 171 HCC patients who underwent anatomical CB (H458) between 2005 and 2020 were collected from 17 expert institutions in a single-arm retrospective study. RESULTS: Morbidities recorded by the International Study Group of Liver Surgery (ISGLS) from grade BC post-hepatectomy liver failure (PHLF) and bile leakage (PHBL), or complications requiring intervention were observed in 37% of patients. A multivariate analysis showed that increased blood loss (iBL) > 1500 mL from PHLF (risk ratio [RR]: 2.79), albumin level < 4 g/dL for PHBL (RR, 2.99), involvement of segment 1, a large size > 6 cm, or compression of the hepatic venous confluence or cava by HCC for all severe complications (RR: 5.67, 3.75, 6.51, and 8.95, respectively) (p < 0.05) were significant parameters. Four patients (3%) died from PHLF. HCC recurred in 50% of 138 surviving patients. The three-year recurrence-free and overall survival rates were 48% and 81%, respectively. CONCLUSIONS: Large tumor size and surrounding tumor involvement, or compression of major vasculatures and the related iBL > 1500 mL were independent risk factors for severe morbidities in patients with HCC undergoing CB.
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Human epidermal growth factor receptor (HER) family proteins are currently major targets of therapeutic monoclonal antibodies against various epithelial cancers. However, the resistance of cancer cells to HER family-targeted therapies, which may be caused by cancer heterogeneity and persistent HER phosphorylation, often reduces overall therapeutic effects. We herein showed that a newly discovered molecular complex between CD98 and HER2 affected HER function and cancer cell growth. The immunoprecipitation of the HER2 or HER3 protein from lysates of SKBR3 breast cancer (BrCa) cells revealed the HER2-CD98 or HER3-CD98 complex. The knockdown of CD98 by small interfering RNAs inhibited the phosphorylation of HER2 in SKBR3 cells. A bispecific antibody (BsAb) that recognized the HER2 and CD98 proteins was constructed from a humanized anti-HER2 (SER4) IgG and an anti-CD98 (HBJ127) single chain variable fragment, and this BsAb significantly inhibited the cell growth of SKBR3 cells. Prior to the inhibition of AKT phosphorylation, BsAb inhibited the phosphorylation of HER2, however, significant inhibition of HER2 phosphorylation was not observed in anti-HER2 pertuzumab, trastuzumab, SER4 or anti-CD98 HBJ127 in SKBR3 cells. The dual targeting of HER2 and CD98 has potential as a new therapeutic strategy for BrCa.
Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/pathology , Receptor, ErbB-2/metabolism , Trastuzumab/pharmacology , Trastuzumab/metabolism , Trastuzumab/therapeutic use , Antibodies, Monoclonal/metabolism , Phosphorylation , Cell Line, TumorABSTRACT
BACKGROUND: Colorectal cancer (CRC) is the most common malignancy in the world, and novel molecular targeted therapies for CRC have been vigorously pursued. We searched for novel combination therapies based on the expression patterns of membrane proteins in CRC cell lines. RESULTS: A positive correlation was observed between the expression of human pidermal growth factor receptor (HER) 3 and mesenchymal-to-epithelial transition factor (MET) on the cell surface of CRC cell lines. The brief stimulation of HER3/MET-high SW1116 CRC cells with both neuregulin-1 (NRG1) and hepatocyte growth factor enhanced ERK phosphorylation and cell proliferation more than each stimulation alone. In addition, a prolonged NRG1 stimulation resulted in the tyrosine phosphorylation of MET. In this context, the Forkhead Box protein M1 (FOXM1)-regulated tyrosine phosphorylation of MET by NRG1 was demonstrated, suggesting the existence of a signaling pathway mediated by FOXM1 upon the NRG1 stimulation. Since the co-expression of HER3 and MET was also demonstrated in in vivo CRC tissues by immunohistochemistry, we investigated whether the co-inhibition of HER3 and MET could be an effective therapy for CRC. We established HER3-and/or MET-KO SW1116 cell lines, and HER3/MET-double KO resulted in the inhibition of in vitro cell proliferation and in vivo tumor growth in nude mice by SW1116 cells. Furthermore, the combination of patritumab, an anti-HER3 fully human mAb, and PHA665752, a MET inhibitor, markedly inhibited in vitro cell proliferation, 3D-colony formation, and in vivo tumor growth in nude mice by SW1116 cells CONCLUSION: The dual targeting of HER3/MET has potential as CRC therapy.
Subject(s)
Colorectal Neoplasms , Humans , Animals , Mice , Mice, Nude , Cell Line, Tumor , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Signal Transduction , Cell Proliferation , TyrosineABSTRACT
BACKGROUND: We have implemented Smart Endoscopic Surgery (SES), a surgical system that uses artificial intelligence (AI) to detect the anatomical landmarks that expert surgeons base on to perform certain surgical maneuvers. No report has verified the use of AI-based support systems for surgery in clinical practice, and no evaluation method has been established. To evaluate the detection performance of SES, we have developed and established a new evaluation method by conducting a clinical feasibility trial. METHODS: A single-center prospective clinical feasibility trial was conducted on 10 cases of LC performed at Oita University hospital. Subsequently, an external evaluation committee (EEC) evaluated the AI detection accuracy for each landmark using five-grade rubric evaluation and DICE coefficient. We defined LM-CBD as the expert surgeon's "judge" of the cystic bile duct in endoscopic images. RESULTS: The average detection accuracy on the rubric by the EEC was 4.2 ± 0.8 for the LM-CBD. The DICE coefficient between the AI detection area of the LM-CBD and the EEC members' evaluation was similar to the mean value of the DICE coefficient between the EEC members. The DICE coefficient was high score for the case that was highly evaluated by the EEC on a five-grade scale. CONCLUSION: This is the first feasible clinical trial of an AI system designed for intraoperative use and to evaluate the AI system using an EEC. In the future, this concept of evaluation for the AI system would contribute to the development of new AI navigation systems for surgery.
Subject(s)
Cholecystectomy, Laparoscopic , Humans , Artificial Intelligence , Bile Ducts , Cholecystectomy, Laparoscopic/methods , Feasibility Studies , Prospective StudiesABSTRACT
The dosage of evocalcet required to control serum parathyroid hormone (PTH) levels varies among secondary hyperparathyroidism (SHPT) patients. This post hoc analysis evaluated the dose-dependent efficacy of evocalcet on serum intact PTH (iPTH) levels, corrected calcium (Ca) and phosphate (P) levels, and safety, in an evaluation period (week 28 to week 30) by stratifying the previous phase 3 data with the final evocalcet dosages (low 1-2 mg [131 patients], medium 3-4 mg [90 patients], high 5-8 mg [92 patients]), and identified pre-treatment patient characteristics predicting the use of higher final evocalcet dosages via univariate and multivariate logistic regression models. At the end of the study at week 30, the median serum iPTH level was higher and the achievement ratio for the target range of Japanese Society for Dialysis Therapy (60-240 pg/mL) was lower in the final high-dose subgroup (216 pg/mL and 58%, respectively) than in the other subgroups (low: 149 pg/mL and 79%; medium: 149 pg/mL and 73%, respectively). Among the three subgroups, the mean serum corrected Ca and P levels demonstrated similar trends, and similar ratio of patients achieved the target range (corrected Ca, 8.4-10 mg/dL; P, 3.5-6.0 mg/dL) from week 28 to week 30. No dose-dependent safety concerns were identified. Younger age, prior cinacalcet use, higher serum levels of iPTH and corrected Ca, procollagen type 1 N-terminal propeptide, intact fibroblast growth factor-23, and larger maximum parathyroid gland volume were significantly associated with final high-dose evocalcet (p < 0.05 in all cases). Patients requiring final high-dose evocalcet had pre-treatment characteristics indicating severe SHPT, leading to a lower final achievement rate for the target PTH levels of Japanese Society for Dialysis Therapy. Therefore, the early initiation of evocalcet treatment for SHPT is critical. Trial registration: This trial was registered as follows: ClinicalTrials.gov: NCT02549391 and JAPIC: JapicCTI-153013.
Subject(s)
Hyperparathyroidism, Secondary , Humans , Calcium , Cinacalcet/therapeutic use , Hyperparathyroidism, Secondary/drug therapy , Hyperparathyroidism, Secondary/etiology , Naphthalenes/therapeutic use , Parathyroid Hormone , Renal DialysisABSTRACT
BACKGROUND: There are multiple surgical procedures for resecting non-ampullary duodenal neoplasms (NADNs), and the appropriate method is selected depending on the tumor location and diagnosis. We herein report 3 cases of NADNs that were resected using pancreas-preserving partial duodenectomy (PPD). CASE REPORTS: The first patient, a 73-year-old woman with a circumferential duodenal adenoma in the supra-ampullary duodenum, underwent surgery. After laparotomy, the duodenum proximal to the tumor was confirmed using intraoperative endoscopy and dissected. The duodenum distal to the tumor was dissected under direct visualization, and the specimen was removed. The distal stump of the duodenum was closed, and duodenojejunostomy was performed as described by Billroth II. The tumor was diagnosed as an adenoma 75 mm in size. She was discharged 12 days after surgery without any complications. The second patient, a 48-year-old man, was diagnosed with a neuroendocrine neoplasm (NEN) with a diameter of 14 mm in the supra-ampullary duodenum. Laparoscopic PPD was performed. He was diagnosed with NEN G1 and discharged the 11th day after surgery. The third patient, a 71-year-old man with a 0-Is + IIa lesion in the horizontal duodenum, underwent surgery. After laparotomy, the horizontal duodenum and proximal jejunum were resected, and duodenojejunostomy was performed. The patient was diagnosed with stage I adenocarcinoma and discharged on the 15th day after surgery. CONCLUSION: PPD is useful for avoiding the morbidity of pancreatoduodenectomy in the management of NADNs without invasion to the ampulla of Vater or pancreas.